Method of placing a tubular membrane on a structural frame

ABSTRACT

The present invention relates to a medical device, and more particularly to a method of forming a tubular membrane on a radially expandable structural frame. In one aspect, a structural frame is placed over a spinning mandrel and a fiber is electro-statically spun over at least a portion of the structural frame forming a membrane. A transfer sheath may be used between the mandrel and structural frame to prevent the electrostatically spun fiber from adhering to the mandrel. In another aspect, a first membrane is spun over the mandrel before the structural frame is placed over the mandrel. In this aspect, at least a portion of the structural frame is sandwiched between the membranes. The membrane or membranes and structural frame form a fiber spun frame assembly. The fiber spun frame assembly may be coated with an elastic polymer. In addition, the membrane or membranes may go through some post processing to achieve desired characteristics or configurations.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional Application Ser.No. 60/379,604, filed May 10, 2002.

FIELD OF THE INVENTION

The present invention relates to a medical device and method of makingthe medical device. In particular, the present invention relates to amedical device having a radially expandable structural frame and atubular membrane structure, and a method of placing the tubular membraneon the radially expandable structural frame.

BACKGROUND OF RELATED ART

The human body has numerous biological valves that control fluid flowthrough body lumens and vessels. For example the circulatory system hasvarious heart valves that allow the heart to act as a pump bycontrolling the flow of blood through the heart chambers veins, andaorta. In addition, the venous system has numerous venous valves thathelp control the flow of blood back to the heart, particularly from thelower extremities.

These valves can become incompetent or damaged by disease, for example,phlebitis, injury, or the result of an inherited malformation. Forexample, heart valves are subject to disorders, such as mitral stenosis,mitral regurgitation, aortic stenosis, aortic regurgitation, mitralvalve prolapse and tricuspid stenosis. These disorder are potentiallylife threatening. Similarly, incompetent or damaged venous valvesusually leak, allowing the blood to improperly flow back down throughveins away from the heart (regurgitation reflux or retrograde bloodflow). Blood can then stagnate in sections of certain veins, and inparticular, the veins in the lower extremities. This stagnation of bloodraises blood pressure and dilates the veins and venous valves. Thedilation of one vein may in turn disrupt the proper function of othervenous valves in a cascading manner, leading to chronic venousinsufficiency.

Numerous therapies have been advanced to treat symptoms and to correctincompetent valves. Less invasive procedures include compression,elevation and wound care. However, these treatments tend to be somewhatexpensive and are not curative. Other procedures involve surgicalintervention to repair, reconstruct or replace the incompetent ordamaged valves, particularly heart valves.

Surgical procedures for incompetent or damaged venous valves includevalvuloplasty, transplantation, and transposition of veins. However,these surgical procedures provide somewhat limited results. The leafletsof venous valves are generally thin, and once the valve becomesincompetent or destroyed, any repair provides only marginal relief.

As an alternative to surgical intervention, drug therapy to correctvalvular incompetence has been utilized. Currently, however, there areno effective drug therapies available.

Other means and methods for treating and/or correcting damaged orincompetent valves include utilizing xenograft valve transplantation(monocusp bovine pericardium), prosthetic/bioprosthetic heart valves andvascular grafts, and artificial venous valves. These means have all hadsomewhat limited results.

What is needed is an artificial endovascular valve for the replacementof incompetent biological human valves, particularly heart and venousvalves. These valves may also find use in artificial hearts andartificial heart assist pumps used in conjunction with hearttransplants.

SUMMARY OF THE INVENTION

The present invention relates to a medical device, and in particular, amethod of placing a tubular membrane on a radially expandable structuralframe. An example of a medical device having a radially expandablestructural frame and a tubular membrane is a stent-based valve.

One embodiment of the radially expandable structural frame comprises aproximal anchor and a distal anchor. The proximal and distal anchors areformed from a lattice of interconnected elements, and have asubstantially cylindrical configuration with first and second open endsand a longitudinal axis extending there between.

The radially expandable structural frame also comprises one or morestruts, each having a first and a second end. The first end of eachstrut is attached to the proximal anchor and the second end of eachstrut is attached to the distal anchor. The tubular membrane assembly isplaced on the radially expandable structural frame.

The present invention provides a method of placing the tubular membraneabout a radially expandable structural frame. In accordance with oneaspect, the method of the present invention comprises forming an innermembrane over a mandrel. The structural frame is radially expanded andplaced over the inner membrane. The radially expanded structural frameis then contracted. An outer membrane is formed over the structuralframe, wherein the inner membrane and outer membrane combine to form thetubular membrane. The tubular membrane may optionally be coated with apolymer. In addition, the tubular membrane may then be processed toachieve desired characteristics.

A medical device having a tubular membrane structure and a radiallyexpandable structural frame is also contemplated by the presentinvention. The medical device comprises an inner membrane formed atleast in part from a polymer, preferably an elastic or elastomericpolymer, and a radially expandable structural frame positioned over theinner membrane. An outer membrane formed at least in part from a polymertube is positioned over the radially expandable structural frame, suchthat the inner membrane and outer membrane combine to form the tubularmembrane structure of the medical device.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows a perspective view of a prosthetic venous valve in thedeployed state according to one embodiment of the present invention.

FIG. 1B shows a perspective view of the prosthetic venous valvestructural frame in the deployed state according to one embodiment ofthe present invention.

FIG. 1C shows a perspective view of the prosthetic venous valvestructural frame having helical connecting members according to oneembodiment of the present invention.

FIG. 1D shows a perspective view of the prosthetic venous valvestructural frame having an hourglass shape according to one embodimentof the present invention.

FIG. 2A shows a perspective view of the proximal stent-based anchor inthe expanded deployed state according to one embodiment of the presentinvention.

FIG. 2B shows a close-up perspective view of a loop having inner andouter radii according to one embodiment of the present invention.

FIG. 2C shows a perspective view of the prosthetic venous valvestructural frame having connecting members connected between theproximal and distal anchors in a peak-to-peak configuration according toone embodiment of the present invention.

FIG. 2D shows a perspective view of the prosthetic venous valvestructural frame having connecting members connected between the distaland proximal anchors in a peak-to-valley configuration according to oneembodiment of the present invention.

FIG. 2E shows a perspective view of the prosthetic venous valvestructural frame having connecting members connected between the distaland proximal anchors in a valley-to-valley configuration according toone embodiment of the present invention.

FIG. 2F shows a perspective view of the prosthetic venous valvestructural frame having connecting members connected between the distaland proximal anchors along the strut members according to one embodimentof the present invention.

FIG. 3 shows a perspective view of the distal stent anchor having aplurality of hoop structures according to one embodiment of the presentinvention.

FIG. 4A is a perspective view illustrating one embodiment of theexpanded (deployed) prosthetic venous valve assembly in the openposition.

FIG. 4B is a section view illustrating one embodiment of the expanded(deployed) prosthetic venous valve assembly in the open position.

FIG. 5A is a perspective view illustrating one embodiment of theexpanded (deployed) prosthetic venous valve assembly in the closedposition.

FIG. 5B is a section view illustrating one embodiment of the expanded(deployed) prosthetic venous valve assembly in the closed position.

FIG. 6A is a perspective view illustrating a membrane limiting meansaccording to one embodiment of the present invention.

FIG. 6B is a perspective view illustrating a membrane limiting meansaccording to one embodiment of the present invention.

FIG. 6C is a perspective view illustrating a membrane limiting meansaccording to one embodiment of the present invention.

FIG. 7 is a flow diagram illustrating the steps to electro-staticallyspin a tubular membrane on a structural frame according to oneembodiment of the present invention.

FIG. 8A is section view illustrating the expanded (deployed) prostheticvenous valve assembly in the open position after some post processingaccording to one embodiment of the present invention.

FIG. 8B shows a close-up section view illustrating a portion of thevalve assembly after some post processing according to one embodiment ofthe present invention.

FIG. 9 is a flow diagram illustrating the steps to electrostaticallyspin a tubular membrane on a structural frame according to oneembodiment of the present invention.

FIG. 10 is a flow diagram illustrating the steps to place a tubularmembrane over a structural frame according to one embodiment of thepresent invention.

FIG. 11 illustrates a sectioned view of a typical vein.

FIG. 12 shows a transverse cross-sectional view of the vein and deployedprosthetic venous valve according to one embodiment of the presentinvention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The stent-based valves of the present invention provide a method forovercoming the difficulties associated with the treatment of valveinsufficiency. Although stent based venous valves are disclosed toillustrate one embodiment of the present invention, one of ordinaryskill in the art would understand that the disclosed invention can beequally applied to other locations and lumens in the body, such as, forexample, coronary, vascular, non-vascular and peripheral vessels, ducts,and the like, including but not limited to cardiac valves, venousvalves, valves in the esophagus and at the stomach, valves in the ureterand/or the vesica, valves in the biliary passages, valves in thelymphatic system and valves in the intestines.

In accordance with one aspect of the present invention, the prostheticvalve is designed to be percutaneously delivered through a body lumen toa target site by a delivery catheter. The target site may be, forexample, a location in the venous system adjacent to an insufficientvenous valve. Once deployed the prosthetic venous valve functions toassist or replace the incompetent or damaged natural valve by allowingnormal blood flow (antegrade blood flow) and preventing or reducingbackflow (retrograde blood flow).

A perspective view of a prosthetic venous valve in the expanded(deployed) state according to one embodiment of the present invention isshown in FIG. 1A. The prosthetic venous valve 100 comprises a structuralframe 101 and a biocompatible membrane assembly 102. In one embodiment,the membrane assembly 102 is comprised of a tubular membrane, valveflaps and valve cusps. The flaps and cusps may be independent componentsattached to the tubular membrane to form the membrane assembly 102, butare preferably part of, and integrated into, the tubular membrane. In apreferred embodiment, the valve flaps and valve cusps are formed intothe tubular membrane by processing techniques as will be discussed ingreater detail below.

For clarity, a perspective view of the prosthetic venous valve 100structural frame 101 is shown in FIG. 1B. The structural frame 101consists of proximal and distal anchor structures 103, 104 connected byat least one connecting member 105. In a preferred embodiment, at leastthree connecting members 105 are utilized.

It should be noted that the terms proximal and distal are typically usedto connote a direction or position relative to a human body. Forexample, the proximal end of a bone may be used to reference the end ofthe bone that is closer to the center of the body. Conversely, the termdistal can be used to refer to the end of the bone farthest from thebody. In the vasculature, proximal and distal are sometimes used torefer to the flow of blood to the heart, or away from the heart,respectively. Since the prosthetic valves described in this inventioncan be used in many different body lumens, including both the arterialand venous system, the use of the terms proximal and distal in thisapplication are used to describe relative position in relation to thedirection of fluid flow. For example, the use of the term proximalanchor in the present application describes the upstream anchor ofstructural frame 101 regardless of its orientation relative to the body.Conversely, the use of the term distal is used to describe the downstream anchor on structural frame 101 regardless of its orientationrelative to the body. Similarly, the use of the terms proximal anddistal to connote a direction describe upstream (retrograde) ordownstream (antegrade) respectively.

The connecting members 105 are attached between the proximal and distalanchors 103, 104 to further support the biocompatible membrane assembly102 (not shown in FIG. 1B). In one embodiment, the connecting members105 are substantially straight members, connecting the stent basedproximal and distal anchors 103, 104 in a direction substantiallyparallel to the longitudinal axis 106. Although three connecting members105 are shown in the illustrated embodiment, this configuration shouldnot be construed to limit the scope of the invention.

Alternatively, the connecting members 105 may be twisted in a helicalfashion as they extend from the proximal to distal anchors 103, 104.This alternate embodiment is illustrated in FIG. 1C. Specifically, theconnection points between the connecting members 105 and the distalanchor 104, and the connecting members 105 and the proximal anchor 103,are rotationally phased 180 degrees from each other to provide thehelical design.

Each connecting member 105 may also be biased inward slightly toward thelongitudinal centerline 106 of the stent-based anchors 103, 104,creating a structural frame 101 having an hour-glass shape with theminimum radius located substantially at the longitudinal midpoint alongthe connecting member 105 length. An hourglass shaped structural frame101 is illustrated in FIG. 1D.

The materials for the structural frame 101 should exhibit excellentcorrosion resistance and biocompatibility. In addition, the materialcomprising the structural frame 101 should be sufficiently radiopaqueand create minimal artifacts during MRI.

The present invention contemplates deployment of the prosthetic venousvalve 100 by both assisted (mechanical) expansion, i.e. balloonexpansion, and self-expansion means. In embodiments where the prostheticvenous valve 100 is deployed by mechanical (balloon) expansion, thestructural frames 101 is made from materials that can be plasticallydeformed through the expansion of a mechanical assist device, such as bythe inflation of a catheter based balloon. When the balloon is deflated,the frame 101 remains substantially in the expanded shape. Accordingly,the ideal material has a low yield stress (to make the frame 101deformable at manageable balloon pressures), high elastic modulus (forminimal recoil), and is work hardened through expansion for highstrength. The most widely used material for balloon expandablestructures 101 is stainless steel, particularly 316L stainless steel.This material is particularly corrosion resistant with a low carboncontent and additions of molybdenum and niobium. Fully annealed,stainless steel is easily deformable.

Alternative materials for mechanically expandable structural frames 101that maintain similar characteristics to stainless steel includetantalum, platinum alloys, niobium alloys, and cobalt alloys. Inaddition other materials, such as polymers and bioabsorbable polymersmay be used for the structural frames 101.

Where the prosthetic venous valve 100 is self-expanding, the materialscomprising the structural frame 101 should exhibit large elasticstrains. A suitable material possessing this characteristic is Nitinol,a Nickel-Titanium alloy that can recover elastic deformations of up to10 percent. This unusually large elastic range is commonly known assuperelasticity.

The disclosure of various materials comprising the structural frameshould not be construed as limiting the scope of the invention. One ofordinary skill in the art would understand that other materialpossessing similar characteristics may also be used in the constructionof the prosthetic venous valve 100. For example, bioabsorbable polymers,such as polydioxanone may also be used. Bioabsorbable materials absorbinto the body after a period of time, leaving only the biocompatiblemembrane 102 in place. The period of time for the structural frame 101to absorb may vary, but is typically sufficient to allow adequate tissuegrowth at the implant location to adhere to and anchor the biocompatiblemembrane 102.

The structural frame 101 may be fabricated using several differentmethods. Typically, the structural frame 101 is constructed from sheet,wire (round or flat) or tubing, but the method of fabrication generallydepends on the raw material form used.

The structural frame 101 can be formed from wire using convention wireforming techniques, such as coiling, braiding, or knitting. By weldingthe wire at specific locations a closed-cell structure may be created.This allows for continuous production, i.e. the components of thestructural frame 101, such as proximal and distal anchors 103, 104, maybe cut to length from a long wire mesh tube. The connecting member 105may then be attached to the proximal and distal anchors 103, 104 bywelding or other suitable connecting means.

In addition, the complete frame structure may be cut from a solid tubeor sheet of material, and thus the structural frame 101 would beconsidered a monolithic unit. Laser cutting, water-jet cutting andphotochemical etching are all methods that can be employed to form thestructural frame 101 from sheet and tube stock.

As discussed above, the disclosure of various methods for constructingthe structural frame 101 should not be construed as limiting the scopeof the invention. One of ordinary skill in the art would understand thatother construction methods may be employed to form the structural frame101 of the prosthetic venous valve 100.

In one embodiment of the invention, the anchors 103, 104 are stent-basedstructures. This configuration facilitates the percutaneous delivery ofthe prosthetic venous valve 100 through the vascular system in acompressed state. Once properly located, the stent-based venous valve100 may be deployed to the expanded state.

A perspective views of a typical stent-based anchor in the expanded(deployed) state is shown in FIG. 2A. Although a Z or S shaped patternstent anchor is shown for the purpose of example, the illustration isnot to be construed as limiting the scope of the invention. One ofordinary skill in the art would understand that other stent geometriesmay be used.

The stent anchors (proximal and distal anchors 103, 104 respectively)each comprise a tubular configuration of structural elements havingproximal and distal open ends and defining a longitudinal axis 106extending therebetween. The stent anchors 103, 104 have a first diameter(not shown) for insertion into a patient and navigation through thevessels, and a second diameter D2 for deployment into the target area ofa vessel, with the second diameter being greater than the firstdiameter. The stent anchors 103, 104, and thus the stent based venousvalve 100, may be either a mechanical (balloon) or self-expanding stentbased structure.

Each stent anchor 103, 104 comprises at least one hoop structure 206extending between the proximal and distal ends. The hoop structure 206includes a plurality of longitudinally arranged strut members 208 and aplurality of loop members 210 connecting adjacent struts 208. Adjacentstruts 208 are connected at opposite ends in a substantially S or Zshaped pattern so as to form a plurality of cells. As previouslydiscussed, one of ordinary skill in the art would recognize that thepattern shaped by the struts is not a limiting factor, and other shapedpatterns may be used. The plurality of loops 210 have a substantiallysemi-circular configuration, having an inter radii 212 and outer radii214, and are substantially symmetric about their centers. The inner andouter radii 212, 214 respectively, are shown in a close-up perspectiveview illustrated in FIG. 2B.

The connecting member 105 may be connected to the proximal and distalanchors 103, 104 at various points along the structure. As illustratedin FIG. 2C, the connecting members 105 are connected between theproximal end of the distal anchor 104 and the distal end of the proximalanchor 103 at the inflection point of the loop members 210. Thisconfiguration creates a “Peak-to-Peak” connection bridging the outerradii 214 of the inflection point of loop members 210 on the proximalanchor 103 with the outer radii 214 of the inflection point of the loopmember 210 on the distal anchor 104.

Preferably the connecting members 105 are connected to the inflectionpoint of loop members 210 oriented directly opposite one another, andare evenly spaced along the circumference of the tubular anchors 103,104. This configuration facilitates the radial expansion of theprosthetic valve from the collapsed (delivered) state to the expanded(deployed) state, and provides a substantially symmetrical valveconfiguration.

Alternatively, the connecting members 105 may be connected between thedistal and proximal anchors 104, 103 to create a “Peak-to-Valley”connection between the loop members 210. In this configuration,illustrated in FIG. 2D, the connecting members 105 are connected to theproximal end of the distal anchor 104 at the outer radii 214 of theinflection point of loop member 210, and the inner radii 212 of theinflection point of loop member 210 on the proximal end of the proximalanchor 103.

In a further embodiment, the connecting members 105 may be connectedbetween the distal end of the distal anchor 104 and the proximal end ofthe proximal anchor 103 at the inflection point of the loop members 210as shown in FIG. 2E. This configuration creates a “Valley-to-Valley”connection bridging the inner radii 212 of the inflection point of loopmembers 210 on the proximal anchor 103 with the inner radii 212 of theinflection point of the loop member 210 on the distal anchor 104.

In still a further embodiment, the connecting members 105 may beconnected between the strut members 208 of the distal anchor 104 and thestrut members 208 of the proximal anchor 103 as shown in FIG. 2F.

In any of the above described configurations, the connections betweenthe connecting members 105 and the anchors 103, 104 may be made at everyinflection point around the circumference of the structure; oralternatively, at a subset of the inflection points around thecircumference of the structure. In other words, connected inflectionpoints alternate with unconnected inflection points in some definedpattern.

Although stent anchors 103, 104 incorporating a singular hoop structureare shown in the embodiment illustrated in FIGS. 2A though 2F, eachstent anchor may utilize a plurality of hoop structures.

FIG. 3 shows a distal anchor having a plurality of hoop structures 306Athrough 306D according to another embodiment of the present invention.In the illustrated embodiment, the distal stent anchor 104 may furthercomprise a plurality of bridge members 314 that connect adjacent hoops306A through 306D. Each bridge member 314 comprises two ends 316A, 316B.One end 316A, 316B of each bridge 314 is attached to one loop on onehoop. Using hoop sections 306C and 306D for example, each bridge member314 is connected at end 316A to loop 310 on hoop section 306C at a point320. Similarly, the opposite end 316B of each bridge member 314 isconnected to loop 310 on hoop sections 306D at a point 321.

The proximal and distal anchors 103, 104 secure the prosthetic valve 100to the inside wall of a body vessel such as a vein, and provide anchorpoints for the connecting members 105. Once deployed in the desiredlocation, the anchors 103, 104 will expand to an outside diameterslightly larger that the inside diameter of the native vessel (notshown) and remain substantially rigid in place, anchoring the valveassembly to the vessel. The connecting members 105 preferably have aninferior radial stiffness, and will conform much more closely to thenative diameter of the vessel, facilitating the operation of thebiocompatible membrane assembly 102.

The membrane assembly is formed from a flexible membrane-likebiocompatible material that is affixed to the frame structure 101. Themembrane must be strong enough to resist tearing under normal use, yetthin enough to provide the necessary flexibility that allows thebiocompatible membrane assembly 102 to open and close satisfactorily.

FIGS. 4A and 4B are perspective and section views, respectively,illustrating one embodiment of the expanded (deployed) prosthetic venousvalve assembly 100 in the open position. The membrane material may be abiological material, such as a vein or small intestine submucosa (SIS),but is preferably a synthetic material such as a polymer, for example anelastic or elastomeric polymer, including a fluoropolymer,fluoroelastomer, or a bioabsorbable material, such as a bioabsorbablepolymer or bioabsorbable elastomer. Bioabsorbable materials may allowcells to grow and form a tissue membrane (or valve flaps) over thebioabsorbable membrane. The bioabsorbable membrane then absorbs into thebody, leaving the tissue membrane and/or flaps in place to act as a newnatural tissue valve.

To achieve the necessary flexibility and strength of the membraneassembly 102, the synthetic material may be reinforced with a fiber,such as an electrostatically spun (ESS) fiber, porous foam, such asePTFE, or mesh. The flexible membrane like biocompatible material isformed into a tube (membrane tubular structure 400) and placed over andaround the structural frame 101. The membrane tubular structure 400 hasa first (distal) and second (proximal) ends 401, 402 respectively, andpreferably also has integrated valve flaps 403 and valve cusps 404.These components together comprise the membrane assembly 102.

The first end 401 of the membrane tubular structure 400 is locatedbetween the proximal and distal anchors 103, 104, and is preferablylocated at the approximate longitudinal midpoint of the connectingmembers 105 between the two anchors 103, 104. The second end 402 of themembrane tubular structure 400 extends proximally from the longitudinalmidpoint, and is preferably located proximal to at least one half of theproximal anchor 103. In one embodiment of the invention, the membranestructure 400 completely covers the proximal anchor 103. Thisconfiguration allows the proximal anchor 103 to expand the membranetubular structure 400 into the native vessel wall, anchoring themembrane tubular structure 400 in place, and providing adequate sealingagainst retrograde blood flow.

The distal end 401 of the membrane tubular structure 400 terminates withthe valve flaps 403. The number of valve flaps 403 is directlyproportional to the number of connecting members 105 supporting themembrane tubular assembly 102. The valve flaps 403 are sufficientlypliable and supple to easily open and close as the blood flow changesfrom antegrade to retrograde. When the valve flaps 403 close (duringretrograde flow) the interior surfaces of the flaps 403 and/or membranetubular structure 400 come into contact to prevent or adequately reduceretrograde blood flow.

To facilitate closing the valve flaps 403 during retrograde blood flow,valve cusps 404 are formed into the membrane tubular structure 400. Thevalve cusps 404 are defined generally by the intersection of theconnecting members 105 and membrane tubular structure 400.

The use of the term “cusps” is not meant to limit the scope of thisinvention. Although the term “cusps” is often more aptly used todescribe the valve members in semilunar valves, such as the aortic andpulmonary valves, this discussion refers to both the cusps of semilunarvalves and the “leaflets” of venous and atrioventricular valves.Accordingly, it should be understood that the aspects discussed inrelation to these valves could be applied to any type of mammalianvalve, including heart valves, venous valves, peripheral valves, etc.

During retrograde flow, blood passes the leading edge of valve flaps 403and enters the valve cusps 404. Since the membrane tubular structure 400(and membrane assembly 102) are substantially sealed against the innervessel wall by proximal anchor 103, the valve cusps 404 form asubstantially fluid tight chamber. As the valve cusps 404 fill, themembrane tubular structure 400 is directed inward until the interiorsurfaces of the membrane tubular structure 400 contact each other,particularly along the leading edges of valve flaps 403, closing themembrane assembly 102. FIGS. 5A and 5B show perspective and sectionviews, respectively, illustrating one embodiment of the expanded(deployed) prosthetic venous valve assembly 100 in the closed position.

In a preferred embodiment of the invention, the membrane assembly 102 isnormally configured in the open position, and only moves to the closedposition upon retrograde blood flow. This configuration minimizesinterference with blood flow (minimized blocking) and reduces turbulenceat and through the valve. The connecting members 105 in this embodimenthave an inferior radial stiffness, and provide a natural bias againstthe movement of the membrane assembly 102 to the closed position. Thisbias assists the valve flaps 403 and valve cusps 404 when returning tothe open position.

Depending on the application, it may also be desired that the biastowards opening the membrane assembly 102 (against closing) besufficiently high to commence opening the valve before antegrade bloodflow begins, i.e. during a point in time when the blood flow is stagnant(there is neither antegrade nor retrograde blood flow), or when minimalretrograde flow is experienced.

In other applications, it may be desirable to have the valve assemblynormally configured in the closed position, biased closed, and only openupon antegrade flow.

As earlier described, the membrane assembly 102 is made from a flexiblemembrane-like biocompatible material formed into the membrane tubularstructure 400. The membrane 400 can be woven, non-woven (such aselectrostatic spinning), mesh, knitted, film or porous film (such asfoam).

The membrane assembly 102 may be fixedly attached to the structuralframe by many different methods, including attachment resulting fromradial pressure of the structural frame 101 against the membraneassembly 102, attachment by means of a binder, heat, or chemical bond,and/or attachment by mechanical means, such as welding or suturing.Preferably some of the membrane assembly 102, such as distal end 402 oftubular membrane 400, is slideably attached to the structural frame 101,particularly along connecting members 105. Allowing the distal end 402to slide along the connecting members 105 may allow or improve theopening and closing of the flaps 403. The sliding movement may alsoassist the cusps 404 when filling and emptying.

In some applications, excessive sliding movement of the membraneassembly 102 is undesirable. In these embodiments, a limiting means maybe integrated into the prosthetic valve 100 to limit the slidingmovement of the membrane assembly 102. Examples of limiting means areshown in FIGS. 6A to 6C. In each embodiment a stop 600 (illustrated asstop 600A, 600B, and 600C in FIGS. 6A to 6C respectively) is integratedinto the connecting member 105. The membrane assembly 102 is wrappedaround the connecting member 105 and bonded to itself to form a loopcollar 605. The loop collar 605 must be sized to inhibit the distal end402 of the membrane assembly 102 from sliding past the stop 600. In FIG.6A, the connecting member 105 has a thickened or “bulbous” sectionforming stop 600A. FIG. 6B illustrates an undulating stop 600Bconfiguration. Similarly, FIG. 6C shows the stop 600C configured as adouble bulbous section. It should be noted that the variousconfigurations illustrated in FIGS. 6A through 6C are exemplary. One ofordinary skill in the art would understand that other configurations ofstops may used.

In one embodiment of the invention the tubular membrane 400 ismanufactured from a fiber reinforced elastomer, such as an elastomericfluoropolymer. The elastomer allows the tubular membrane 400 to beextremely thin and elastic, while the fiber provides the necessarystrength. One method used to produce this type of reinforced membranevalve is an Electro-Static Spinning (ESS) process.

The ESS process can be used to form a tubular membrane on many differenttypes of structural frames, including frames associated with stents,stent grafts, valves, including percutaneously delivered venous valve,AAA (Abdominal Aortic Aneurysm) devices, local drug delivery devices,and the like. The disclosure of the ESS process for forming the tubularmembrane 400 on the structural frame of a stent-based venous valve isexemplary, and thus not meant to limit the scope of this invention.

FIG. 7 shows the steps for electrostatically spinning a reinforcedtubular membrane onto a structural frame according to one embodiment ofthe present invention. The ESS process comprises first placing atransfer sheath over a spinning mandrel as shown in step 700. Thetransfer sheath is a thin material that is used to prevent the ESS spunfiber from adhering to the mandrel. In instances where the mandrelitself is not electrically conducting, the transfer sheet may alsoprovide the necessary electrical conductivity to attract the ESS spunfiber.

In one embodiment of the invention, the transfer sheath comprises a thinpolymer tube, preferably fluoropolymer, of such a thickness that it canbe easily deformed, and preferably collapsed, so that it is capable ofbeing withdrawn conveniently from the lumen of the structural frame 101and/or membrane tubular structure 400. The use of a transfer sheath madeof other fibrous or sheet materials, such as other polymer, polymeric ormetallic materials is not excluded. Most preferably, the transfer sheathwill be made of an ePTFE tube.

To enhance electrical conductivity and reduce the time it takes to buildup the ESS layer, the ePTFE tube may be first coated with gold on atleast a portion of the interior surface before placing the tube on themandrel. This process may be completed by coating the inside of thetube, but is preferably done by coating the exterior of the ePTFE tubeand then inverting the tube so that the gold coating is on the interiorsurface. The process may also be completed by inverting the tube so thatthe interior surface to be coated is exposed on exterior of the tube,coating the now exposed interior surface, and the inverting the tube sothat the interior coated surface is back on the inside of the tube.

It should be noted that under certain circumstances it may not benecessary to use the transfer sheath. Such circumstances may include,for example, where the spinning mandrel is electrostatically conductingand has a surface or surface treatment that will prevent the ESS spunfiber from adhering to the mandrel.

In a preferred embodiment, the spinning mandrel is electricallyconducting, and more preferably, is a metal coated with Teflon®.However, electrical conduction may not be essential. In such embodimentsthe spinning mandrel may be of any suitable material, including plasticmaterial. Non-conductors may be used so long as the charge is capable ofbeing transferred (i.e. bleed off) onto the transfer sheet or throughthe material itself.

The spinning mandrel may be hollow or solid, and preferably has a smoothsurface to facilitate sliding between the transfer sheath and mandrelduring removal. However, it may be desirable to maintain some degree offrictional resistance between the transfer sheath and mandrel to reduceslippage between the two components during the ESS process.

The valve structural frame 101 is then placed on the transfer sheath,step 710, and the ESS fiber is spun directly onto the valve structuralframe 101 as shown in step 720. Preferably, the structural frame 101 isconfigured in the expanded or deployed state prior to placing thestructural frame 101 on the spinning mandrel. This is generally the casewhen the structural frame 101 is of the self-expanding design. In otherembodiments, such as balloon-expandable designs, the expansion mechanismmay be integrated within the spinning mandrel to expand the structuralframe during the spinning process.

The expandable mandrel may also be used for electro-statically spinninga fiber onto a self-expanding structural frame 101. In such instances,the self-expanding structural frame 101 is placed on the spinningmandrel in the expanded state, and the expansion mechanism on theexpandable mandrel is mandrel activated to further radially expand thestructural frame to a “super-expanded” state. ESS fiber is then spundirectly onto the super-expanded structural frame 101. The largerdiameter of the super-expanded structural frame 101 allows more materialto be deposited on the structural frame, which may result in less postprocessing procedures. Post processing is described in step 760.

Electro-static spinning of a fiber is generally known in the art, andtypically involves creating an electrical potential between a sourcecomponent, i.e. the fiber or preferably a fiber forming liquid, and adownstream component, i.e. the spinning mandrel, transfer sheath orstructural frame. The electrical potential causes the source component,typically the fiber forming liquid, to be attracted to, and thus movetowards, the downstream component.

The electrical potential is created by providing an electrical charge toeither the source or downstream component, and grounding the othercomponent. Preferably, the source component will receive an electricalcharge, while the downstream component is grounded.

Many different methods are known in the art for producing an electricalcharge on a source component. In one embodiment, a fiber forming liquidis introduced into an electric field, whereby the fiber forming liquidis caused to produce a charged fiber. In another, more preferredembodiment, a device (introducer device) introducing the fiber formingliquid into the process is electrically charged, thus causing the fiberforming liquid to assume a like charge.

Several methods may be used to introduce the fiber forming liquid intothe process, including spraying the fiber forming liquid from a nozzle,or injecting the fiber forming liquid from a needle, orifice or driptube. In a preferred embodiment, the fiber forming liquid issufficiently viscous to be extruded into the process with an extrusiondevice.

Once the fiber forming liquid is introduced into the process, it ishardened to form the ESS fiber. Hardening of the liquid into an ESSfiber may be accomplished, for example, by cooling the liquid until thefiber forming liquid will not lose its fibrous shape. Other methods forhardening the fiber may also include hardening by introducing a chemicalhardener into the fiber forming liquid, or directing an air stream overthe electrically drawn fiber forming liquid stream. In a preferredembodiment, a polymer is put into solution with a solvent to form aviscous fiber forming liquid. As the fiber forming liquid is drawn fromthe introducer device, the solvent comes out of solution forming thepolymer fiber.

Various drying techniques may be applied to evaporate the solvent andbring the polymer out of solutions. Drying techniques may include, forexample, applying heat or airflow to or over the coated fiber spun frameassembly. In addition, the solvent may dry naturally without applyingartificial drying techniques.

The viscosity of the fiber forming liquid may be adjusted based on thematerial used for the source component, and the percent solids desiredas the source component reaches the downstream component. Typicalconcentrations range from 2 to 100 percent. The choice of concentrationdepends on the material, its molecular weight, the solvent efficiency,and temperature. The concentration and temperature also control thediameter of the fiber. These viscosities will typically produce a fiberat the downstream component having percent solids in the range of about95 percent to about 100 percent, and preferably over 99 percent. This isdesirable in order to produce structures that contain entangled or pointbonded fibers. Concentrations lower than 95 percent can be used if it isdesired to allow filaments to fuse together into a sheet-like barrierstructure.

The hardened fiber is then collected onto the structural frame.Collecting of the fiber involves attracting the ESS fiber to thedownstream component (i.e. spinning mandrel, transfer sheath orstructural frame) of the ESS system, while spinning the downstreamcomponent. In a preferred embodiment, where the source component iselectrically charged, a downstream component is grounded to complete theelectric potential between the source and downstream component, and thusattract the ESS fiber. In other embodiments, a downstream component maybe electrically charged to attract the ESS fiber where the sourcecomponent is grounded. In still other embodiments, various combinationsof downstream components may be electrically charged to enhanceelectrical conductivity and reduce the time it takes to build up the ESSlayer.

Particular ESS fibers suitable for this spinning process includefluoropolymers, such as a crystalline fluoropolymer with an 85/15%(weight/weight ratio) of vinylidene fluoride/hexafluoropropylene(VDF/HFP). Solvay Solef® 21508 and Kynarflex 2750-01 are two suchexamples. However, one of skill in the art would understand that anymaterial possessing the desired characteristics may be used, including,for example: bioabsorbable polymers, such as polyglycolic acid,polylactic acid, poly (paradioxanone), polycaprolactone, poly(trimethylenecarbonate) and their copolymers; and semicrystallinebioelastomers, such as 60/40% (weight/weight ratio) of polylacticacid/polycaprolactone (PLA/PCL), 65/35 (weight/weight ratio) ofpolyglycolic acid/polycaprolactone (PGA/PCL), or nonabsorbablesiliconized polyurethane, non-siliconized polyurethanes, siliconizedpolyureaurethane, including siliconized polyureaurethane end capped withsilicone or fluorine end groups, or natural polymers in combinationthereof. It should be noted that poly(trimethylenecarbonate) can not bespun as a homopolymer.

The spinning process should be continued until an ESS fiber tube, orfabric, is formed having a wall thickness of between 5 μm and 100 μm ormore, preferably, approximately 20 μm. The ESS fiber spun structuralframe 101 is then removed from the spinning mandrel, step 730, beforethe transfer sheath is removed from the fiber spun frame, step 740. Oncethis step is completed, the fiber spun structural frame is coated in asolution of polymer, such as fluoroelastomer, as shown in step 750.

Several different methods may be utilized to perform the coating processon the fiber spun structural frame, including spray coating with an airor airless sprayer, dip coating, chemical vapor deposition, plasmacoating, co-extrusion coating, spin coating and insert molding. In stillanother preferred embodiment, the fiber spun structural frame is firstdip coated in a polymer solution, and then spun about its longitudinalaxis to more evenly distribute the coating. In this embodiment, thefiber spun structural frame is not first removed from the spinningmandrel. Instead, the frame/mandrel assembly is dip coated and spunbefore removing the fiber spun structural frame from the spinningmandrel. Still other methods for coating the fiber spun structural framewould be obvious to one of skill in the art.

The coating process may act to encapsulate and attach at least a portionof the spun ESS reinforcement fiber to the structural frame 101. Itshould be noted that it in some embodiments of the invention, somemovement between the membrane assembly 102 and the structural frame 101is desired. Accordingly, not all of the ESS fiber spun structural framemay be coated.

The coating process may also remove some porosity of the membranematerial. However, it may be desirable to maintain some porosity inparticular embodiments to promote biological cell grown on and withinthe membrane tubular structure.

The coating solution preferably comprises a polymer put into solutionwith a solvent. As the solvent evaporates, the polymer comes out ofsolution forming the coating layer. Accordingly, for the process to workproperly, the solvent used in the coating solution should not dissolveor alter the ESS fibers being coated. By way of example, a coatingsolution of 60/40% VDF/HFP in methanol (methanol being the solvent) hasbeen found to be a suitable solution for coating an ESS fiber comprisedof 85/15% VDF/HFP.

In one embodiment of the invention, the polymer comprising the coatingis Daikin's Dai-El G701BP, which is a 60/40% VDF/HFP. In addition,Daikin's Dai-El T630, a thermoplastic elastomer based on vinylidenefluoride/hexafluoropropylene/tetrafluoroethylene (VDF/HFP/TFE) can alsobe used. Again, one of ordinary skill in the art would understand thatother materials having suitable characteristics may be used for thecoating, for example, other polymers, such as siliconized polyurethane,including Polymer Technology Group's Pursil, Carbosil, Purspan andPurspan F.

The coating process may be repeated until the desired characteristicsand thickness are achieved. For venous valves a thickness of between 12μm and 100 μm and preferably between 25 μm and 50 μm has been found tobe acceptable.

Once the coating process is complete some post processing of themembrane tubular structure 400 may take place to achieve particulardesired characteristics or configurations. This may include creating thefinal form of the membrane assembly 102. The post processing step isshown as optional step 760 in FIG. 7.

The post processing step 760 may be used to form or shape, for example,a valve cusp, similar to cusp 404, in the membrane tubular structure400. In addition, post processing may change the characteristics of themembrane tubular structure 400 by thickening or thinning the membrane inparticular locations. Thickening the membrane may add rigidity andreinforcement to a particular area. Thinning the membrane may make themembrane more pliable, which is a desirable characteristic for the valveflaps 403. Still other post processing procedures may change thephysical shape of the membrane tubular structure 400, for example, byforming the loop collar 605 along the distal edge of membrane tubularstructure 400. The loop collar 605 may assist in controlling themovement (translational and circumferential) of the membrane assembly102 along the connecting members 105. The loop collars 605 may alsoreduce fatigue and tear stresses in the membrane.

FIGS. 8A and 8B show an example of the result of a post processing stepthat forms a loop collar 605 according to one embodiment of the presentinvention. To achieve this result, the membrane tubular structure 400 iswrapped around at least one element of structural frame 101 (connectingmember 105) and bonded to itself at bond point 800.

Another method for electrostatically spinning a tubular membrane onto aradially expandable structural frame according to another embodiment ofthe present invention is shown in FIG. 9. Although similar to theprocess described above, this alternative method provides an ESS spunmembrane on the inside, as well as the outside of the structural frame.The inner and outer ESS spun membranes may mechanically adhere to eachother, and in a sense encapsulated the structural frame. Thisconfiguration provides some additional features, including having asmoother interior surface that reduces turbulence, improves flowdynamics and lowers the chance of thrombosis formation.

Similar to the embodiment described earlier, the ESS process comprisesfirst placing a transfer sheath over a spinning mandrel as shown in step900. It should be noted that under certain circumstances it may not benecessary to use the transfer sheath. Such circumstances may include,for example, where the spinning mandrel is electro-statically conductingand has a surface or surface treatment that will prevent the ESS spunfiber from adhering to the mandrel.

An ESS fiber is then spun directly onto the transfer sheath creating aninner coat membrane as shown in step 910. The ESS process shouldcontinue until an ESS tube is formed having a wall thickness of between2 μm and 50 μm or more, and preferably, approximately 20 μm. Aspreviously stated, the inner coat membrane covers some or all of theinterior surface of structural frame 101. The structural frame 101 isthen radially expanded and placed over the inner coat membrane on thespinning mandrel as shown in step 920. Expansion of the structural frame101 may be achieved by several different methods. One method includestaking advantage of the thermal and shape memory characteristics ofparticular materials. For example, shape memory materials, such asNitinol, possess little or no recoil ability when cooled, but exhibit ahigh degree of memory, i.e. the ability to return to a configured shape,when heated. Cooling the Nitinol structural frame 101 before expansionallows the structural frame to remain in the expanded configurationuntil being heated. Accordingly, the Nitinol structural frame 101 can becooled, expanded, and then placed over the inner coat membrane. Once inplace, the structural frame can be heated to activate the Nitinol memorycharacteristics, causing the Nitinol structural frame 101 to contract tothe pre-expansion size and configuration.

The structural frame 101 is sized such that when configured in theexpanded or deployed state, it will fit tightly over the inner coatmembrane on the spinning mandrel. To fit the structural frame 101 overthe inner coat membrane, the structural frame 101 may have to beradially expanded (“super-expanded”) to a diameter slightly larger thanthe expanded deployed state to allow the structural frame 101 to fitover the inner coat membrane.

Once the structural frame 101 is placed over the inner coat membrane,another ESS fiber is spun directly onto the structural frame, as shownin step 930, to form a top-coat membrane. The ESS process shouldcontinue until the topcoat membrane tube is formed having a wallthickness of between 2 μm and 50 μm or more, and preferably,approximately 20 μm. The top-coat membrane may cover and adhere to theinner coat membrane through the interstitial spaces between the elementsthat comprise the structural frame 101.

As stated in an earlier described embodiment of the invention, thestructural frame 101 is configured on the mandrel in the expandeddeployed state prior to spinning the top-coat membrane. In otherembodiments, it may be desirable to expand (super expand) the structuralframe 101 on the spinning mandrel during or prior to the spinningprocess. This procedure may alter the configuration and properties ofthe spun membrane, resulting in less post processing of the membrane.Post processing is described in step 960.

The structural frame 101, with the inner coat and top coat membranes, isthen removed from the spinning mandrel, as shown in step 940, and coatedwith a solution of highly elastic polymer as shown in step 950. Asstated previously, the coating process may be achieved using severaldifferent coating methods, including spin coating, spray coating, dipcoating, chemical vapor deposition, plasma coating, co-extrusion coatingand insert molding.

As previously described, a representative elastomeric polymer is. afluoroelastomer. The coating process may be repeated until the desiredcharacteristics and thickness are achieved. For a venous valveapplication, a thickness of between 12 μm and 100 μm, and preferablybetween 25 μm and 50 μm, has been found to be acceptable.

Once the coating process is complete, some post processing of thetubular membrane may take place, as shown as an optional step 960 inFIG. 9.

Although each of the above described ESS methods spin the fiber directlyon to the structural frame, one of ordinary skill in the art wouldunderstand that a tubular membrane may also be spun separately, and thenplaced over the structural frame 101 by known methods.

Another, more preferred method for forming the membrane material overand around the structural frame 101 is shown in FIG. 10. As describedearlier, this method is presented in the context of a prosthetic valveapplication. However, the method may be applied generally to anyapplication where a micro-cellular foam or pourous material,particularly an ePTFE membrane, needs to be placed over and around aradially expandable structural frame. Exemplary structural frames mayinclude stents, stents grafts, valves (including percutaneouslydelivered venous valves), AAA (Abdominal Aortic Aneurysm) devices, localdrug delivery devices, and the like. Accordingly, the disclosed deviceis not meant to limit the scope of the inventive method.

In this embodiment, a tubular structure is fabricated from a polymermaterial that can be processed such that it exhibits an expandedcellular structure, preferably expanded Polytetrafluoroethylene (ePTFE).The ePTFE tubing is made by expanding Polytetrafluoroethylene (PTFE)tubing, under controlled conditions, as is well known in the art. Thisprocess alters the physical properties that make it satisfactory for usein medical devices. However, one of ordinary skill in the art wouldunderstand that other materials that possess the necessarycharacteristics could also be used.

The method comprises first placing a transfer sheath over a mandrel asshown in step 1000. As described earlier, the transfer sheath is a thinmaterial that is used to prevent the tubing and coating from adhering tothe mandrel. The transfer sheath may be made of sheet metal, metal foil,or polymer sheet, such as for example Polytetrafluoroethylene (PTFE).Preferably, the transfer sheath will be made of a material that can beeasily deformed, and preferably collapsed so that it can be withdrawnconveniently from the lumen of the tube once the process is complete.

The transfer sheath/mandrel combination are then coated in a solution ofhighly elastic polymer, such as fluoroelastomer, as shown in step 1010,to form an inner membrane. As stated previously, the coating may beapplied using various methods, including, for example, spin coating,spray coating, dip coating, chemical vapor deposition, plasma coating,co-extrusion coating and insert molding.

In one embodiment of the invention, the coating solution comprises apolymer put into solution with a solvent, such as methanol. In addition,most solvents can be used with expanded Polytetrafluoroethylene (ePTFE).

In a preferred embodiment of the invention, the polymer comprising thecoating includes Daikin's Dai-El T630, a thermoplastic elastomer basedon vinylidene fluoride/hexafluoropropylene/tetrafluoroethylene(VDF/HFP/TFE) and blends thereof. Other preferred polymers includesiliconized polyurethanes, including silicone-urethane copolymers, andblends thereof. Silicone-urethane copolymers can consist of segmentedpolyetherurethane with aromatic urea as hard segments and poly(tetramethyleneoxide) [PTMO] as soft segments. Silicone (20 to 25%) isadded by replacing PTMO with polydimethylsiloxane, and fluorine (0.5 to2%) can be added by surface-modifying end groups. Again, one of ordinaryskill in the art would understand that other materials having suitablecharacteristics may be used for the coating, for example, other polymersand blends thereof. Preferred siliconized polyurethanes include PolymerTechnology Group's Pursil, Carbosil, Purspan and Purspan F.

The coating process should continue until the inner membrane achieves awall thickness of between 6 μm and 100 μm or more, preferably between 12μm to 25 μm.

In an alternate embodiment, a polymer tube, preferably an ePTFE tube,may be expanded and placed over the sheath/mandrel combination (step1015), before being contracted (step 1020). Expansion may be by anysuitable expansion means known in the art, including mechanicalexpansion, such as by means of a balloon expansion device or expandablecage, expansion by utilizing a tapered mandrel (i.e. sliding the polymertube over a tapered mandrel of increasing diameter), etc. In additionother means may be used in conjunction with the expansion means toassist placing the tube over the sheath mandrel combination. Theseassist means may include, for example, thermally expanding the tube withheat, or chemically expanding the tube with a solvent. These methods areknown in the art.

Contraction of the tube is typically done by reversing the method usedto expand the tube. For example, ePTFE is naturally elastic. If theePTFE tube was expanded by a mechanical expansion means, removing theexpansion means would allow the ePTFE tube to contract towards itpre-expansion configuration. In addition the contraction of the tube maybe enhanced by applying heat or chemicals (solvents).

Once the tube is expanded over the sheath/mandrel, the whole assemblymay be coated with a solution of highly elastic polymer, such asfluoroelastomer as shown in step 1025 to form the inner membrane. Thecoating process is similar to that shown in step 1010 above, and may beachieved by any method known in the art capable of achieving the desiredresult, including spin coating, spray coating, dip coating, chemicalvapor deposition, plasma coating, co-extrusion coating and insertmolding.

The coating process described in step 1025 should continue until theinner membrane described in the alternate embodiment is coated with apolymer base having a wall thickness of between 6 μm and 100 μm or more,preferably between 12 μm to 25 μm.

The structural frame 101 is then radially expanded and positioned overthe inner membrane as shown in step 1030. The structural frame 101 maybe radially expanded using any know expansion means, including a balloonexpansion device or frame expansion device. In one embodiment of theinvention, the structural frame 101 is constructed from a shape memoryalloy, such as Nitinol. As previously described, Nitinolcharacteristically holds a deformed shaped when cooled, and returns toits original shape when heated. Accordingly, it is possible to hold aNitinol structural frame 101 in the radially expanded state by coolingthe frame before the expansion means is removed. This will facilitateplacement of the Nitinol structural frame over the inner membrane.

The structural frame 101 may then be radially contracted over the innermembrane, as shown in step 1040. It is desirable to maintain a slightinterference fit between the structural frame 101 and the innermembrane. The method to radially contract the structural frame 101 maydepend on the material and type of construction of the structural frame101, and is not meant to limit the scope of the invention. As describedabove, a structural frame 101 constructed from a shape memory alloy,such as Nitinol, can be radially contracted (to the pre-expanded andcooled size) by heating. Depending on the material used, other methodsthat may also be employed to radially contract the structural frameinclude, simply removing the expansion means providing the radialexpansion force, or applying a compressive force about the structuralframe 101. Still other methods to radially contract the structural frame101 would be obvious to one of skill in the art.

Once the structural frame 101 is contracted over the inner membrane, asecond polymer tube, preferably an ePTFE tube, is expanded and placedover the structural frame, as shown in step 1050, forming an outermembrane. The tube is then contracted into position as shown in step1060. As described earlier, the tube may be expanded by severaldifferent means, including mechanical, thermal, or chemical (solvents)expansion. Similarly, contraction of the tube may be accomplished by themethods described in step 1020.

In embodiments where two separate ePTFE tubes are used for the inner andouter membranes, as described in steps 1015 and 1050 respectively, eachtube should have a wall thickness of between 25 μm and 50 μm beforeexpansion; yielding a wall thickness of between 6 μm and 10 μm afterexpansion and placement. It should be noted that these membranes may ormay not be bonded together. If only a single ePTFE tube is used for theouter membrane only, as described in step 1050 (not following alternatesteps 1015 through 1025), the tube should have a wall thickness beforeexpansion of between 50 μm and 100 μm; yielding a wall thickness afterexpansion of between 12 μm and 20 μm.

The inner and outer membranes combine to for a membrane structure. Inthe valve example described above, the membrane structure wouldrepresent membrane tubular structure 400, while the structural framewould represent the structural frame 101.

Once the membrane structure is formed, some or all of the assembly maybe optionally coated with a solution of a highly elastic polymer, suchas an elastomeric polymer, as shown in step 1070. The coating may beapplied by any method known in the art, including spin coating, spraycoating, dip coating, chemical vapor deposition, plasma coating,co-extrusion coating and insert molding.

As described earlier (see step 1010) the coating solution may be afluoroelastomer. In one embodiment of the invention, the coating isDaikin Dai-El T630, a thermoplastic elastomer based on vinylidenefluoride/hexafluoropropylene/tetrafluoroethylene (VDF/HFP/TFE) andblends thereof. Again, one of ordinary skill in the art would understandthat other materials having suitable characteristics might be used forthe coating, for example, other polymers, such as siliconizedpolyurethane.

The coating process should continue until the coating achieves a wallthickness of between 6 μm and 100 μm or more, preferably between 12 μmto 25 μm.

Once the coating process is complete, some post processing of themembrane structure may take place to achieve particular desiredcharacteristics or configurations. This post processing step is shown asoptional step 1080 in FIG. 10.

By way of example, for valve applications, the post processing step 1080may be used to form or shape valve cusps, similar to cusps 404, or valveflaps, such as flaps 403, in the membrane structure. In addition, postprocessing may change the characteristics of the membrane structure bythickening or thinning the membrane in particular locations. Thickeningthe membrane may add rigidity and reinforcement to a particular area.Thinning the membrane may make the membrane more pliable. Still otherpost processing procedures may change the physical shape of the membranestructure, for example, by forming the loop collar 605 along the distaledge of membrane assembly 102. The loop collar 605 may assist incontrolling the translational and circumferential movement of themembrane assembly 102 along the connecting members 105. The loop collars605 may also reduce fatigue and tear stresses in the membrane.

It is important to note that the local delivery of drug/drugcombinations may be utilized to treat a wide variety of conditionsutilizing any number of medical devices, or to enhance the functionand/or life of the device. Medical devices that may benefit from thistreatment include, for example, the frame based unidirectional flowprosthetic implant subject of the present invention.

Accordingly, in addition to the embodiments described above, therapeuticor pharmaceutic agents may be added to any component of the deviceduring fabrication, including, for example, the ESS fiber, polymer orcoating solution, membrane tube, structural frame or inner and outermembrane, to treat any number of conditions. In addition, therapeutic orpharmaceutic agents may be applied to the device, such as in the form ofa drug or drug eluting layer, or surface treatment after the device hasbeen formed. In a preferred embodiment, the therapeutic and pharmaceuticagents may include any one or more of the following:antiproliferative/antimitotic agents including natural products such asvinca alkaloids (i.e. vinblastine, vincristine, and vinorelbine),paclitaxel, epidipodophyllotoxins (i.e. etoposide, teniposide),antibiotics (dactinomycin (actinomycin D) daunorubicin, doxorubicin andidarubicin), anthracyclines, mitoxantrone, bleomycins, plicamycin(mithramycin) and mitomycin, enzymes (L-asparaginase which systemicallymetabolizes L-asparagine and deprives cells which do not have thecapacity to synthesize their own asparagine); antiplatelet agents suchas G(GP) ll_(b)/lll_(a) inhibitors and vitronectin receptor antagonists;antiproliferative/antimitotic alkylating agents such as nitrogenmustards (mechlorethamine, cyclophosphamide and analogs, melphalan,chlorambucil), ethylenimines and methylmelamines (hexamethylmelamine andthiotepa), alkyl sulfonates-busulfan, nirtosoureas (carmustine (BCNU)and analogs, streptozocin), trazenes-dacarbazinine (DTIC);antiproliferative/antimitotic antimetabolites such as folic acid analogs(methotrexate), pyrimidine analogs (fluorouracil, floxuridine, andcytarabine), purine analogs and related inhibitors (mercaptopurine,thioguanine, pentostatin and 2-chlorodeoxyadenosine {cladribine});platinum coordination complexes (cisplatin, carboplatin), procarbazine,hydroxyurea, mitotane, aminoglutethimide; hormones (i.e. estrogen) ;anticoagulants (heparin, synthetic heparin salts and other inhibitors ofthrombin); fibrinolytic agents (such as tissue plasminogen activator,streptokinase and urokinase), aspirin, dipyridamole, ticlopidine,clopidogrel, abciximab; antimigratory; antisecretory (breveldin);anti-inflammatory: such as adrenocortical steroids (cortisol, cortisone,fludrocortisone, prednisone, prednisolone, 6α-methylprednisolone,triamcinolone, betamethasone, and dexamethasone), non-steroidal agents(salicylic acid derivatives i.e. aspirin; para-aminophenol derivativesi.e. acetominophen; indole and indene acetic acids (indomethacin,sulindac, and etodalac), heteroaryl acetic acids (tolmetin, diclofenac,and ketorolac), arylpropionic acids (ibuprofen and derivatives),anthranilic acids (mefenamic acid, and meclofenamic acid), enolic acids(piroxicam, tenoxicam, phenylbutazone, and oxyphenthatrazone),nabumetone, gold compounds (auranofin, aurothioglucose, gold sodiumthiomalate); immunosuppressives: (cyclosporine, tacrolimus (FK-506),sirolimus (rapamycin), azathioprine, mycophenolate mofetil); angiogenicagents: vascular endothelial growth factor (VEGF), fibroblast growthfactor (FGF); angiotensin receptor blockers; nitric oxide donors;anti-sense oligionucleotides and combinations thereof; cell cycleinhibitors, mTOR inhibitors, and growth factor receptor signaltransduction kinase inhibitors; retenoids; cyclin/CDK inhibitors; HMGco-enzyme reductase inhibitors (statins); and protease inhibitors.

As earlier disclosed, the present invention relates to a medical device,particularly a stent-based valve, to be delivered and deployed in a bodylumen or vessel. One typical use of this disclosed stent-based valve isto assist or replace insufficient venous valves in the vascular system.

A sectioned view of a typical vein is illustrated in FIG. 11. The vein1100 may be any of the tubular branching vessels that carry blood fromthe capillaries toward the heart (antegrade blood flow). Vein 1100comprises a vein wall 1101 formed of three layers.

The innermost layer of the vein wall 1101 is the Tunica Intima 1102. TheIntima 1102 is a simple epithelium made up of a single layer of flatepithelial cells comprising connective and elastic tissue. The secondand main portion of the vein wall 1101 is the Tunica Media 1103. TheMedia 1103 is made up of a combination of smooth muscle and elastictissue. The smooth muscle portion of the Media 1103 is usually largerthan the other layers and consequently provides support to counteractoutward radial force caused by blood pressure within the vessel. To someextent, the Media 1103 also provides support against the radialexpansion of the prosthetic venous valve 100. Finally, the third layerof the vein wall 1101 is the outer surface or the Tunica Adventitia1104. The Adventitia 1104 is comprised generally of connective tissue,but may also include arties and veins that supply the tissues of thevessel.

In addition, veins greater than approximately two (2) millimeters indiameter located below the heart often have one or more natural valves1105 at intervals to prevent reflux of the blood (retrograde bloodflow). These venous valves 1105 are necessary to counteract the effectof gravitation force on antegrade blood flow.

When the prosthetic venous valve 100 of the present invention isdeployed into position, the proximal and distal anchors 103, 104 expandinto the vein wall 1101, and engage the Tunica Intima 1102. A transversecross-sectional view of an open prosthetic venous valve 100 deployedinto vein 1100 during antegrade blood flow is shown in FIG. 12.

The correct placement of the anchors 103, 104 may result in mounds oftissue 1200 protruding between the strut members comprising the distalanchor 104 after the anchor 104 has been embedded in the Tunica Intima1102. These tissue mounts 1200 retain endothelial cells that can providefor the re-endothelialization of the vessel wall. Endothelialregeneration of the vessel wall may cause endothelial cells to migrateto, and over the anchor 104 members, resulting in a thin tissue layerencapsulating the anchor 104 struts. This endothelialization may assistin anchoring the prosthetic venous valve 100 in place.

Continued tissue growth or neointima and/or intimal hyperplasia throughthe openings of the expanded structural frame 101 meshes as a result oftissue injury may cause vessel restenosis. As described earlier, todeter or control neointimal hyperplasia, the structural frame 101 may becoated or treated with a therapeutic or pharmaceutic agent, such as ananti-restenotic (antiproliferative). Similarly, the membrane assembly102 may be coated or impregnated with a therapeutic or pharmaceuticagent.

The embodiment illustrated in FIG. 12 depicts the biocompatible membraneassembly 102 located on the exterior surface of the proximal anchor 103and connecting members 105. In this configuration, the correct placementof the proximal anchor 103 expands the exterior surface of thebiocompatible membrane assembly 102 into the Tunica Intima 1102,creating a substantially fluid tight seal between the membrane assembly102 and vein wall 1101. This sealing effect substantially eliminatesblood flow around the exterior of the prosthetic venous valve 100. Inaddition, the sealing effect facilitates the membrane assembly 102closing during retrograde blood flow.

While a number of variations of the invention have been shown anddescribed in detail, other modifications and methods of use contemplatedwithin the scope of this invention will be readily apparent to those ofskill in the art based upon this disclosure. It is contemplated thatvarious combinations or subcombinations of the specific embodiments maybe made and still fall within the scope of the invention. For example,the embodiments variously shown to be prosthetic “venous valves” may bemodified to instead incorporate prosthetic “heart valves” and are alsocontemplated. Moreover, all assemblies described are believed usefulwhen modified to treat other vessels or lumens in the body, inparticular other regions of the body where fluid flow in a body vesselor lumen needs to be controlled or regulated. This may include, forexample, the coronary, vascular, non-vascular and peripheral vessels andducts. Accordingly, it should be understood that various applications,modifications and substitutions may be made of equivalents withoutdeparting from the spirit of the invention or the scope of the followingclaims.

The following claims are provided to illustrate examples of somebeneficial aspects of the subject matter disclosed herein which arewithin the scope of the present invention.

1. A method of placing a tubular membrane structure about a radiallyexpandable structural frame, the method comprising the steps of: placinga transfer sheath over a mandrel; coating the transfer sheath with anelastomeric polymer solution to form an inner membrane; radiallyexpanding the structural frame; placing the radially expanded structuralframe over the inner membrane; contracting the radially expandedstructural frame; and forming an outer membrane over the structuralframe, the inner membrane and outer membrane combining to form thetubular membrane.
 2. The method of claim 1 wherein the step of coatingcomprises spraying the polymer solution over the transfer sheath.
 3. Themethod of claim 1 wherein the step of coating comprises dipping themandrel in the polymer solution.
 4. The method of claim 1 where the stepof coating comprises: dipping the mandrel in the solution of polymer;and spinning the dip coated mandrel to evenly distribute the coating. 5.A method of placing a tubular membrane structure about a radiallyexpandable structural frame, the method comprising the steps of: placinga transfer sheath over a mandrel; placing a polymer tube over thetransfer sheath; coating the polymer tube with an elastomeric polymer toform an inner membrane; radially expanding the structural frame; placingthe radially expanded structural frame over the inner membrane;contracting the radially expanded structural frame; and forming an outermembrane over the structural frame, the inner membrane and outermembrane combining to form the tubular membrane.
 6. The method of claim5 wherein the step of placing a polymer tube over the transfer sheathcomprises: radially expanding the polymer tube; positioning the radiallyexpanded polymer tube over the transfer sheath; and contracting theradially expanded polymer tube onto the transfer sheath.
 7. The methodof claim 5 wherein the step of coating comprises spraying the polymersolution over the polymer tube.
 8. The method of claim 5 wherein thestep of coating comprises dipping the polymer tube in the polymersolution.
 9. The method of claim 5 where the step of coating comprises:dipping the polymer tube in the polymer solution; and spinning the dipcoated polymer tube to evenly distribute the coating.
 10. The method ofclaim 1 or 5 wherein the step of radially expanding the structural framecomprises: inserting a radially expanding means into the structuralframe along the structural frame's longitudinal axis; and radiallyexpanding the expanding means to expand the structural frame.
 11. Themethod of claim 10 further comprising cooling the radially expandedstructural frame in the expanded position to substantially maintain theexpanded position.
 12. The method of claim 1 or 5 wherein the step ofcontracting the radially expanded structural frame comprises applying aradially compressive force to the structural frame.
 13. The method ofclaim 1 or 5 wherein the step of contracting the radially expandedstructural frame comprises heating the structural frame.
 14. The methodof claim 1 or 5 wherein the step of forming an outer membrane over thestructural frame comprises: radially expanding a polymer tube;positioning the radially expanded polymer tube over the structuralframe; and contracting the radially expanded polymer tube onto thetransfer sheath.
 15. The method of claim 1 or 5 further comprisingcoating the tubular membrane with a polymer solution.
 16. The method ofclaim 15 wherein the step of coating comprises spraying the polymersolution over the tubular membrane.
 17. The method of claim 15 whereinthe step of coating comprises dipping the tubular membrane in thepolymer solution.
 18. The method of claim 15 where the step of coatingcomprises: dipping the tubular membrane in the polymer solution; andspinning the dip coated tubular membrane to evenly distribute thecoating.
 19. The method of claim 1 or 5 further comprising performingpost processing of the tubular membrane.
 20. The method of claim 19wherein the step of post processing includes reshaping the tubularmembrane.
 21. The method of claim 19 wherein the step of post processingincludes thinning at least a portion of the tubular membrane.
 22. Themethod of claim 19 wherein the step of post processing includesthickening at least a portion of the tubular membrane.
 23. The method ofclaim 19 wherein the step of post processing includes forming cusps inthe tubular membrane.